The Tell-Tale Brain

mutant gene expresses itself to a greater degree, in more brain regions, in some synesthetes than in others. But how exactly does the mutation cause cross-wiring? We know that the normal brain does not come ready-made with neatly packaged areas that are clearly delineated from each other. In the fetus there is an initial dense overproliferation of connections that get pruned back as development proceeds. One reason for this extensive pruning process is presumably to avoid leakage (signal spread) between adjacent areas, just as Michelangelo whittled away excess marble to produce David. This pruning is largely under genetic control. It’s possible that the synesthesia mutation leads to incomplete pruning between some areas that lie close to each other. The net result would be the same: cross-wiring.

However, it is important to note that anatomical cross-wiring between brain areas cannot be the complete explanation for synesthesia. If it were, how could you account for the commonly reported emergence of synesthesia during the use of hallucinogenic drugs such as LSD? A drug can’t suddenly induce sprouting of new axon connections, and such connections would not magically vanish after the drug wore off. Thus it must be enhancing the activity of preexisting connections in some way—which is not inconsistent with the possibility that synesthetes have more of these connections than the rest of us. David Brang and I also encountered two synesthetes who temporarily lost their synesthesia when they started taking antidepressant drugs called selective serotonin reuptake inhibitors (SSRIS), a drug family that famously includes Prozac. While subjective reports cannot entirely be relied on, they do provide valuable clues for future studies. One person was able to switch her synesthesia on or off by starting or stopping her drug regimen. She detested the antidepressant Wellbutrin because it deprived her of the sensory magic that synesthesia provided; the world looked drab without it.

I have been using the word “cross-wiring” somewhat loosely, but until we know exactly what’s going on at the cellular level, the more neutral term “cross-activation” might be better. We know, for instance, that adjacent brain regions often inhibit each other’s activity. This inhibition serves to minimize crosstalk and keeps areas insulated from one other. What if there were a chemical imbalance of some kind that reduces this inhibition—say, the blocking of an inhibitory neurotransmitter, or a failure to produce it? In this scenario there would not be any extra “wires” in the brain, but the synesthete’s wires would not be properly insulated. The result would be the same: synesthesia. We know that, even in a normal brain, extensive neural connections exist between regions that lie far apart. The normal function of these is unknown (as with most brain connections!), but a mere strengthening of these connections or a loss of inhibition might lead to the kind of cross-activation I suggest.

In light of the cross-activation hypothesis we can now also start to guess why Francesca had such powerful emotional reactions to mundane textures. All of us have a primary touch map in the brain called the primary somatosensory cortex, or S1. When I touch you on the shoulder, touch receptors in your skin detect the pressure and send a message to your S1. You feel the touch. Similarly when you touch different textures, a neighboring touch map, S2, is activated. You feel the textures: the dry grain of a wooden deck, the slippery wetness of a bar of soap. Such tactile sensations are fundamentally external, originating from the world outside your body.

Another brain region, the insula, maps internal feelings from your body. Your insula receives continuous streams of sensation from receptor cells in your heart, lungs, liver, viscera, bones, joints, ligaments, fascia, and muscles, as well as from specialized receptors in your skin that sense heat, cold, pain, sensual touch, and perhaps tickle and itch as well. Your insula uses this information to represent how you feel in relation to the outside world and your immediate environment. Such sensations are fundamentally internal, and comprise the primary ingredients of your emotional state. As a central player in your emotional life, your insula sends signals to and receives signals from other emotional centers in your brain including the amygdala, the autonomic nervous system (powered by the hypothalamus), and the orbitofrontal cortex, which is involved in nuanced emotional judgments. In normal people these circuits are activated when they touch certain emotionally charged objects. Caressing, say, a lover, could generate complex feelings of ardor, intimacy, and pleasure. Squeezing a lump of feces, in contrast, likely leads to strong feelings of disgust and revulsion. Now think of what would happen if there were an extreme exaggeration of these very connections linking S2, the insula, the amygdala, and the orbitofrontal cortex. You would expect to see precisely the sort of touch-triggered complex emotions that Francesca experiences when she touches denim, silver, silk, or paper—things that would leave most of us unmoved.

Incidentally, Francesca’s mother also has synesthesia. But in addition to emotions, she reports taste sensations in response to touch. For example, caressing a wrought-iron fence evokes an intense salty flavor in her mouth. This too makes sense: The insula receives strong taste input from the tongue.

WITH THE IDEA of cross-activation we seemed to be homing in on a neurological explanation for number-color and textural synesthesia.³ But as other synesthetes showed up in my office, we realized there are many more forms of the condition. In some people, days of the week or months of the year produced colors: Monday might be green, Wednesday pink, and December yellow. No wonder many scientists thought they were crazy! But, as I said earlier, I’ve learned over the years to listen to what people say. In this particular case, I realized that the only thing days of the week, months, and numbers have in common is the concept of numerical sequence or ordinality. So in these individuals, unlike Becky and Susan, perhaps it is the abstract concept of numerical sequence that evokes the color, rather than the visual appearance of the number. Why the difference between the two types of synesthetes? To answer this, we have to return to brain anatomy.

After the shape of a number is recognized in your fusiform, the message is relayed further on to your angular gyrus, a region in your parietal lobes involved, among other things, in higher color processing. The idea that some types of synesthesia might involve the angular gyrus is consistent with an old clinical observation that this structure is involved in cross-sensory synthesis. In other words, it is thought that this is a grand junction where information about touch, hearing, and vision flow together to enable the construction of high-level percepts. For example, a cat purrs and is fluffy (touch), it purrs and meows (hearing), and it has a certain appearance (vision) and fishy breath (smell)—all of which are evoked by the memory of a cat or the sound of the word “cat.” No wonder patients with damage here lose the ability to name things (anomia) even though they can recognize them. They have difficulty with arithmetic, which, if you think about it, also involves cross-sensory integration: in kindergarten you learn to count with your fingers, after all. (Indeed, if you touch the patient’s finger and ask her which one it is, she often can’t tell you.) All of these bits of clinical evidence strongly suggest that the angular gyrus is a great center in the brain for sensory convergence and integration. So perhaps it’s not so outlandish, after all, that a flaw in the circuitry could lead to colors being quite literally evoked by certain sounds.

According to clinical neurologists, the left angular gyrus in particular may be involved in juggling numerical quantity, sequences, and arithmetic. When this region is damaged by stroke, the patient can recognize numbers and can still think reasonably clearly, but he has difficulty with even the simplest arithmetic. He can’t subtract 7 from 12. I have seen patients who cannot tell you which of two numbers—3 or 5—is larger.

Here we have the perfect arrangement for another type of cross-wiring. The angular gyrus is involved in color processing and numerical sequences. Could it be that, in some synesthetes, the crosstalk occurs between these two higher areas near the angular gyrus rather than lower down in the fusiform? If so, that would explain why, in them, even abstract number representations or the idea of a number prompted by days of the week or months will strongly manifest color. In other words, depending on which part of the brain the abnormal synesthesia gene is expressed, you get different types of synesthetes: “higher” synesthetes driven by numerical concept, and “lower” synesthetes driven by visual appearance alone. Given the multiple back-and-forth connections between brain areas, it is also possible that numerical ideas about sequentiality are sent back down to the fusiform gyrus to evoke colors.

In 2003 I began a collaboration with Ed Hubbard and Geoff Boynton from the Salk Institute for Biological